Anuesrhesiu, 1979, Volume 34, pages 1016-101 9 CASE R E P O R T
Acute amphetamine abuse Problems during general anaesthesia for neurosurgery
ROSALIND MICHEL
Amphetamine is one of the most potent sympathomimetic amines in respect ofstimulation of the central nervous system. The drug may therefore be expected to lighten the depth of anaesthesia or to increase the required dosage of anaesthetic agents. The following case report illustrates the difficulties that may arise during anaesthesia in a patient taking amphetamines.
Case report The patient, a fit girl of 22 years of age and weighing 62.2 kg, was involved in an accident when she drove her car into a tree. She was admitted with a head injury to a distinct general hospital where a laceration of her forehead was sutured, her skull was X-rayed and she was admitted for observation overnight. She had retrograde amnesia for 1 hr and posttraumatic amnesia for 12 hr. The next day the patient appeared well and she was discharged home. However, at this stage no-one had reported on the skull X-rays. About a week after the accident the radiologist’s report revealed a depressed skull fracture which involved the frontal sinus with air present within the cranial cavity. The patient was recalled to hospital and referred to the neurosurgical unit of the teaching hospital. She appeared well, her forehead wound was healed and she needed a great deal of persuasion to accept
AND
A.P. ADAMS
further treatment. She was immediately admitted for surgical elevation of her fracture but she discharged herself from hospital that evening. During that afternoon she had had many rather strange visitors. The patient’s general practitioner finally persuaded her to accept surgical treatment and the patient was admitted 5 days later for craniotomy. On admission she appeared well and no abnormal physical signs, except a bony depression of her forehead were found. The arterial pressure was 108/60 mmHg and the pulse rate was not apparently recorded. Medication consisted of sulphadiazine l g 6-hourly, penicillin 500 mg, 6-hourly for the 5 preceeding days and the patient was believed to have continued taking these drugs. Premedication consisted of oral diazepam 10 mg 1 hr preoperatively. Anaesthesia was induced with thiopentone 300 mg, pancuronium 7 mg and fentanyl 50 fig. After laryngoscopy the larynx was sprayed with about 60 mg of 10% lignocaine and the trachea was intubated with a No. 8 ‘Flotex’oral tube. An intravenous infusion of Hartmann’s solution was started, a radial artery cannula was inserted for arterial pressure measurement and connected to a Simonsen and Wee1 transducer, amplifier and display system. A nasopharyngeal temperature probe was also inserted. Anaesthesia was maintained with 33% oxygen in nitrous oxide and supplements of fentanyl (Fig. 1). Intermittent positive pressure
R. Michel, MB, BS, FFARCS, Senior Registrar, A.P. Adams, PhD, MB, BS, FFARCS, Consultant Anaesthetist and Clinical Lecturer, Nuffield Department of Anaesthetics, Radcliffe Infirmary, Oxford OX2 6HE. Communications should be addressed to Dr A.P. Adams who is now Professor of Anaesthetics, Guy’s Hospital, London S.E.1.
1016
0003-2409/79/1200-1016~02.00 0 1979 Blackwell Scientific Publications
Acute amphetamine abuse
1017
from automatic to manual control. Two mg pancuronium, 80 mg frusemide, 10 mg droperidol, were given intravenously with little effect. Repeat blood gas analysis showed Pao, 27.7 kPa, Paco, 4.13 kPa, pH 7.40 and base excess -4.7 mmol/l. The tenseness of the dura was not improved and the anaesthetist’s suspicions of amphetamine abuse were aroused by a previous experience during dental anaesthesia. The anaesthetist telephoned the patient’s general practitioner who reported ‘she had tried everything in the way of sex and drugs’. Although the risks of halothane on ICP were appreciated, 0.5% halothane from a Fluotec Mk 2 vaporiser was introduced into the anaesthetic gas mixture and this procedure produced a dramatic improvement in the operating conditions and reduction in systemic arterial pressures and heart rate (Fig. I). The operation then proceeded uneventfully. Arterial blood was taken for assay of suspected stimulants including amphetamine. However, the result proved negative, which was not an entirely unexpected finding because of the limitations of the assay and the fact that over 98% of a dose of amphetamine is held in tissues other than blood. Unfortunately a urine sample was not obtained until 18 hr later and this sample
ventilation of the lungs was maintained with an Oxford ventilator in conjunction with a Bain circuit fed with a fresh gas flow of 4.5 litreslmin; tidal volume was 950 ml at a frequency of 12 respirations/min. Anaesthesia proceeded uneventfully apart from a persistent tachycardia of 110-130 beats/min which necessitated. after checking the anaesthetic machine, the supply of fresh gases and the patient’s ventilation, three increments of 100 pg fentanyl so that 400 Lcg had been given within the first hour of anaesthesia. Two increments of 1 and 2 mg of pancuronium to a total dose of 10 mg had also been given within the first hour of anaesthesia. During this time 2.0 g sulphadiazine was given slowly intravenously. After l a hr of anaesthesia routine arterial blood gases were measured: Paoz 27.6 kPa, Paco, 5.06 kPa, pH 7.33, Base excess-5.5 mmol/litre. About 15 min later the surgeon had exposed the dura mater but the intracranial pressure was so great that there was concern about impending infarction of the brain. The patient had a raised arterial pressure and heart rate and her skin was hot and sweaty; the nasopharyngeal temperature, however, was 37°C. The anaesthetic circuit was changed for another similar circuit and ventilation changed Hr
I500 I
1700
1600 I
I
I
I
I
I
l
I
I800 l
1
3(10
I
I
Thiopentone, mg
?
I
I?O
120
? yo
?
‘20
Pancuronium, rng Fentanyl pg Halolhane 0.5%
1
8P
Induction, of onosthesia
Frusemide, rng Droperidol, rng ?Atropine 0.6 rng Neostigmine 2 . 5 rng
[Hortrnann’s solution
Sudden rise in intracranial pressure
FIG. I . Anaesthetic record of patient described in text. The results of the arterial blood-gas samples taken at points A are given in the text.
1018
R. Michel and A.P. Adams
also proved negative. The patient made an excellent recovery and, although she was judged by everyone to be a rather strange ‘junky’ character, she later presented the surgeon and his assistant, but not the anaesthetists, with bottles of whisky.
Discussion In man, the depth of anaesthesia produced by 0.5 g amylobarbitone sodium given intra-
venously can be lessened by the injection of 10-30 mg amphetamine intravenously. The effect of amphetamine taken orally may last for 7 hr. These effects include raised arterial systolic, diastolic and pulse pressures. The heart rate may be reflexly slow. Amphetamines are significantly abused by the drug-taking population of society and cases similar to that described here may occur not infrequently. If this patient had undergone laparotomy rather than craniotomy, she would probably have been less efficiently monitored, the surgeon would not have been aware of the rise in intracranial pressure and the incident might have passed unremarked. Racemic amphetamine has been used in veterinary medicine in the treatment of barbiturate toxicity. Hatch studied the effect of amphetamines on thiopentone anaesthesia in dogs.’ He found that the duration of anaesthesia was halved and the ambulation time was also markedly reduced. The effect was observed with racemic amphetamine and both the d- and fisomers, suggesting that both dopamine and noradrenaline synaptic transmissions are facilitated. Hatch and Ruch found similar shortening of ketamine anaesthesia in cats following amphetamine administration.2 L-amphetamine was far more effective in antagonising anaesthesia than d-amphetamine. Johnston ef a1.j studied halothane requirements in dogs after acute administration of dexamphetamine. In all their studies the halothane requirements as judged by minimum alveolar concentration (MAC) were raised, and there was a profound rise in systolic arterial pressure above control readings. Cardiac irregularities which included atrial, nodal and ventricular ectopic beats were observed. However, after chronic administration of dexamphetamine, the halothane requirement was reduced and there was no change in arterial pressure or heart rhythm. It has been shown that
noradrenaline is released into the central nervous system, presumably from adrenergic nerve terminals, after amphetamines are taken.4 This may explain the increased anaesthetic requirement. After prolonged amphetamine usage, the central nervous system catecholamines are depleted, and so anaesthetic requirements may fall. Although this patient was seen pre-operatively by the anaesthetist no history of current drug therapy was obtained other than medications prescribed by her doctors. The patient, freely and without prompting as to the nature of the drug, volunteered intermittent amphetamine abuse once her operation was over and it is possible that her visitors had kept her supplied with the drug. However, despite tactful questioning, she was unwilling to reveal the exact nature and dose she had taken before her anaesthetic; recognized proprietary preparations include ‘purple hearts’, ‘green hearts’, ‘blues’ (Drinamyl, Dexytal, dextroamphetamine with amylobarbitone) and combinations of amphetamines with quinalbarbitone (goof balls). Her initial self-discharge from hospital may also be relevant in this respect, The failure to detect amphetamines or other stimulants in the blood or urine was due to the samples not being taken early enough; a urine sample taken at the time of the anaesthetic might have yielded a positive result. The possibility that drugs similar to amphetamine, such as )hose taken by patients for slimming, might produce similar untoward effects during anaesthesia should be borne in mind.
Acknowledgments The authors wish to thank Dr R.A. Moore of the Nuffield Department of Clinical Biochemistry for his help. S-rY A case of unsuspected acute amphetamine abuse by a 22-year-old girl which led to serious intracranial hypertension during anaesthesia for a neurosurgical procedure is described. It was difficult to maintained anaesthesia with a n intermittent positive-pressure ventilation technique using muscle relaxants, NzO and Oz and and supplements of fentanyl despite large doses of pancuronium and fentanyl. The differing
Acute amphetamine abuse effects of chronic and acute amphetamine dosage on anaesthetic requirements are reviewed. Key words ANALEPTICS, amphetamine, addiction. SURGERY, neurosurgery.
References 1. HATCH, R.C. (1973) Experiments on antagonism of
barbiturate anesthesia with adrenergic, serotonergic
1019
and cholinergic stimulants given alone and in combination. American Journal of Veterinary Research, 34, 1321-1331. 2. HATCH,R.C. & RUCH,T. (1974) Experiments on antagonism of ketamine anaethesia in cats given adrenergic, serotonergic and cholinergic stimulants alone and in combination. American Journal of Veterinary Rsearch, 35, 35-39. 3. JOHNSTON,R.R., WAY,W.L. & MILLER, R.D.(1 972) Alteration of anestnetic requirement by amphetamine. Anesthesia 36, 357-363. 4. CARR,L.A. & MOORE,K.E. (1969) Norepinephrine release from brain by d-amphetamine in uiuo. Science, 164, 322-323.
Acute amphetamine abuse Problems during general anaesthesia for neurosurgery
ROSALIND MICHEL
Amphetamine is one of the most potent sympathomimetic amines in respect ofstimulation of the central nervous system. The drug may therefore be expected to lighten the depth of anaesthesia or to increase the required dosage of anaesthetic agents. The following case report illustrates the difficulties that may arise during anaesthesia in a patient taking amphetamines.
Case report The patient, a fit girl of 22 years of age and weighing 62.2 kg, was involved in an accident when she drove her car into a tree. She was admitted with a head injury to a distinct general hospital where a laceration of her forehead was sutured, her skull was X-rayed and she was admitted for observation overnight. She had retrograde amnesia for 1 hr and posttraumatic amnesia for 12 hr. The next day the patient appeared well and she was discharged home. However, at this stage no-one had reported on the skull X-rays. About a week after the accident the radiologist’s report revealed a depressed skull fracture which involved the frontal sinus with air present within the cranial cavity. The patient was recalled to hospital and referred to the neurosurgical unit of the teaching hospital. She appeared well, her forehead wound was healed and she needed a great deal of persuasion to accept
AND
A.P. ADAMS
further treatment. She was immediately admitted for surgical elevation of her fracture but she discharged herself from hospital that evening. During that afternoon she had had many rather strange visitors. The patient’s general practitioner finally persuaded her to accept surgical treatment and the patient was admitted 5 days later for craniotomy. On admission she appeared well and no abnormal physical signs, except a bony depression of her forehead were found. The arterial pressure was 108/60 mmHg and the pulse rate was not apparently recorded. Medication consisted of sulphadiazine l g 6-hourly, penicillin 500 mg, 6-hourly for the 5 preceeding days and the patient was believed to have continued taking these drugs. Premedication consisted of oral diazepam 10 mg 1 hr preoperatively. Anaesthesia was induced with thiopentone 300 mg, pancuronium 7 mg and fentanyl 50 fig. After laryngoscopy the larynx was sprayed with about 60 mg of 10% lignocaine and the trachea was intubated with a No. 8 ‘Flotex’oral tube. An intravenous infusion of Hartmann’s solution was started, a radial artery cannula was inserted for arterial pressure measurement and connected to a Simonsen and Wee1 transducer, amplifier and display system. A nasopharyngeal temperature probe was also inserted. Anaesthesia was maintained with 33% oxygen in nitrous oxide and supplements of fentanyl (Fig. 1). Intermittent positive pressure
R. Michel, MB, BS, FFARCS, Senior Registrar, A.P. Adams, PhD, MB, BS, FFARCS, Consultant Anaesthetist and Clinical Lecturer, Nuffield Department of Anaesthetics, Radcliffe Infirmary, Oxford OX2 6HE. Communications should be addressed to Dr A.P. Adams who is now Professor of Anaesthetics, Guy’s Hospital, London S.E.1.
1016
0003-2409/79/1200-1016~02.00 0 1979 Blackwell Scientific Publications
Acute amphetamine abuse
1017
from automatic to manual control. Two mg pancuronium, 80 mg frusemide, 10 mg droperidol, were given intravenously with little effect. Repeat blood gas analysis showed Pao, 27.7 kPa, Paco, 4.13 kPa, pH 7.40 and base excess -4.7 mmol/l. The tenseness of the dura was not improved and the anaesthetist’s suspicions of amphetamine abuse were aroused by a previous experience during dental anaesthesia. The anaesthetist telephoned the patient’s general practitioner who reported ‘she had tried everything in the way of sex and drugs’. Although the risks of halothane on ICP were appreciated, 0.5% halothane from a Fluotec Mk 2 vaporiser was introduced into the anaesthetic gas mixture and this procedure produced a dramatic improvement in the operating conditions and reduction in systemic arterial pressures and heart rate (Fig. I). The operation then proceeded uneventfully. Arterial blood was taken for assay of suspected stimulants including amphetamine. However, the result proved negative, which was not an entirely unexpected finding because of the limitations of the assay and the fact that over 98% of a dose of amphetamine is held in tissues other than blood. Unfortunately a urine sample was not obtained until 18 hr later and this sample
ventilation of the lungs was maintained with an Oxford ventilator in conjunction with a Bain circuit fed with a fresh gas flow of 4.5 litreslmin; tidal volume was 950 ml at a frequency of 12 respirations/min. Anaesthesia proceeded uneventfully apart from a persistent tachycardia of 110-130 beats/min which necessitated. after checking the anaesthetic machine, the supply of fresh gases and the patient’s ventilation, three increments of 100 pg fentanyl so that 400 Lcg had been given within the first hour of anaesthesia. Two increments of 1 and 2 mg of pancuronium to a total dose of 10 mg had also been given within the first hour of anaesthesia. During this time 2.0 g sulphadiazine was given slowly intravenously. After l a hr of anaesthesia routine arterial blood gases were measured: Paoz 27.6 kPa, Paco, 5.06 kPa, pH 7.33, Base excess-5.5 mmol/litre. About 15 min later the surgeon had exposed the dura mater but the intracranial pressure was so great that there was concern about impending infarction of the brain. The patient had a raised arterial pressure and heart rate and her skin was hot and sweaty; the nasopharyngeal temperature, however, was 37°C. The anaesthetic circuit was changed for another similar circuit and ventilation changed Hr
I500 I
1700
1600 I
I
I
I
I
I
l
I
I800 l
1
3(10
I
I
Thiopentone, mg
?
I
I?O
120
? yo
?
‘20
Pancuronium, rng Fentanyl pg Halolhane 0.5%
1
8P
Induction, of onosthesia
Frusemide, rng Droperidol, rng ?Atropine 0.6 rng Neostigmine 2 . 5 rng
[Hortrnann’s solution
Sudden rise in intracranial pressure
FIG. I . Anaesthetic record of patient described in text. The results of the arterial blood-gas samples taken at points A are given in the text.
1018
R. Michel and A.P. Adams
also proved negative. The patient made an excellent recovery and, although she was judged by everyone to be a rather strange ‘junky’ character, she later presented the surgeon and his assistant, but not the anaesthetists, with bottles of whisky.
Discussion In man, the depth of anaesthesia produced by 0.5 g amylobarbitone sodium given intra-
venously can be lessened by the injection of 10-30 mg amphetamine intravenously. The effect of amphetamine taken orally may last for 7 hr. These effects include raised arterial systolic, diastolic and pulse pressures. The heart rate may be reflexly slow. Amphetamines are significantly abused by the drug-taking population of society and cases similar to that described here may occur not infrequently. If this patient had undergone laparotomy rather than craniotomy, she would probably have been less efficiently monitored, the surgeon would not have been aware of the rise in intracranial pressure and the incident might have passed unremarked. Racemic amphetamine has been used in veterinary medicine in the treatment of barbiturate toxicity. Hatch studied the effect of amphetamines on thiopentone anaesthesia in dogs.’ He found that the duration of anaesthesia was halved and the ambulation time was also markedly reduced. The effect was observed with racemic amphetamine and both the d- and fisomers, suggesting that both dopamine and noradrenaline synaptic transmissions are facilitated. Hatch and Ruch found similar shortening of ketamine anaesthesia in cats following amphetamine administration.2 L-amphetamine was far more effective in antagonising anaesthesia than d-amphetamine. Johnston ef a1.j studied halothane requirements in dogs after acute administration of dexamphetamine. In all their studies the halothane requirements as judged by minimum alveolar concentration (MAC) were raised, and there was a profound rise in systolic arterial pressure above control readings. Cardiac irregularities which included atrial, nodal and ventricular ectopic beats were observed. However, after chronic administration of dexamphetamine, the halothane requirement was reduced and there was no change in arterial pressure or heart rhythm. It has been shown that
noradrenaline is released into the central nervous system, presumably from adrenergic nerve terminals, after amphetamines are taken.4 This may explain the increased anaesthetic requirement. After prolonged amphetamine usage, the central nervous system catecholamines are depleted, and so anaesthetic requirements may fall. Although this patient was seen pre-operatively by the anaesthetist no history of current drug therapy was obtained other than medications prescribed by her doctors. The patient, freely and without prompting as to the nature of the drug, volunteered intermittent amphetamine abuse once her operation was over and it is possible that her visitors had kept her supplied with the drug. However, despite tactful questioning, she was unwilling to reveal the exact nature and dose she had taken before her anaesthetic; recognized proprietary preparations include ‘purple hearts’, ‘green hearts’, ‘blues’ (Drinamyl, Dexytal, dextroamphetamine with amylobarbitone) and combinations of amphetamines with quinalbarbitone (goof balls). Her initial self-discharge from hospital may also be relevant in this respect, The failure to detect amphetamines or other stimulants in the blood or urine was due to the samples not being taken early enough; a urine sample taken at the time of the anaesthetic might have yielded a positive result. The possibility that drugs similar to amphetamine, such as )hose taken by patients for slimming, might produce similar untoward effects during anaesthesia should be borne in mind.
Acknowledgments The authors wish to thank Dr R.A. Moore of the Nuffield Department of Clinical Biochemistry for his help. S-rY A case of unsuspected acute amphetamine abuse by a 22-year-old girl which led to serious intracranial hypertension during anaesthesia for a neurosurgical procedure is described. It was difficult to maintained anaesthesia with a n intermittent positive-pressure ventilation technique using muscle relaxants, NzO and Oz and and supplements of fentanyl despite large doses of pancuronium and fentanyl. The differing
Acute amphetamine abuse effects of chronic and acute amphetamine dosage on anaesthetic requirements are reviewed. Key words ANALEPTICS, amphetamine, addiction. SURGERY, neurosurgery.
References 1. HATCH, R.C. (1973) Experiments on antagonism of
barbiturate anesthesia with adrenergic, serotonergic
1019
and cholinergic stimulants given alone and in combination. American Journal of Veterinary Research, 34, 1321-1331. 2. HATCH,R.C. & RUCH,T. (1974) Experiments on antagonism of ketamine anaethesia in cats given adrenergic, serotonergic and cholinergic stimulants alone and in combination. American Journal of Veterinary Rsearch, 35, 35-39. 3. JOHNSTON,R.R., WAY,W.L. & MILLER, R.D.(1 972) Alteration of anestnetic requirement by amphetamine. Anesthesia 36, 357-363. 4. CARR,L.A. & MOORE,K.E. (1969) Norepinephrine release from brain by d-amphetamine in uiuo. Science, 164, 322-323.
